The Glyoxalase 1 – Methylglyoxal Pathway Regulates Neurite Development of Cerebral Cortical Neurons in the Mammalian Brain

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dc.contributor.advisorYang, Guang
dc.contributor.authorMohammad, Lamees
dc.contributor.committeememberGuo, Jiami
dc.contributor.committeememberMcFarlane, Sarah
dc.contributor.committeememberHuang, Carol T.L.
dc.date2020-11
dc.date.accessioned2020-05-15T21:50:10Z
dc.date.available2020-05-15T21:50:10Z
dc.date.issued2020-05
dc.description.abstractNewborn neurons of the mammalian cerebral cortex undergo substantial morphological changes during development. Neurite elongation and branching are crucial morphological changes in early neuronal development that are necessary for the formation of dendrites and axons – structural elements that allow neurons to communicate with each other and form circuits. One factor that has received little attention as a possible regulator of neurite development is metabolism. In this thesis, I show that methylglyoxal, an intermediate metabolite of glycolysis, and its metabolizing enzyme, glyoxalase 1 (Glo1) regulate the elongation and branching of neurites. Knockdown of Glo1 expression using short-hairpin RNA or inhibiting the enzymatic activity of Glo1 in cultured mouse cortical neurons reduces neurite length and impairs branching organization. Furthermore, I found that knockdown or inhibition of Glo1 activity perturbs development of both excitatory projection neurons and inhibitory interneurons. When neurons are treated with excessive methylglyoxal, morphological perturbation is recapitulated. These results suggest a link between methylglyoxal metabolism and neuronal development and provide the foundation for future studies of the molecular mechanisms that mediate this metabolic regulation.en_US
dc.identifier.citationMohammad, L. (2020). The Glyoxalase 1 – Methylglyoxal pathway regulates neurite development of cerebral cortical neurons in the mammalian brain (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.en_US
dc.identifier.doihttp://dx.doi.org/10.11575/PRISM/37851
dc.identifier.urihttp://hdl.handle.net/1880/112064
dc.language.isoengen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen
dc.rightsUniversity of Calgary graduate students retain copyright ownership and moral rights for their thesis. You may use this material in any way that is permitted by the Copyright Act or through licensing that has been assigned to the document. For uses that are not allowable under copyright legislation or licensing, you are required to seek permission.en_US
dc.subjectNeurite developmenten_US
dc.subjectneurite branchingen_US
dc.subjectmetabolismen_US
dc.subjectglyoxalase 1en_US
dc.subjectmethylglyoxalen_US
dc.subjectexcitatory projection neuronsen_US
dc.subject.classificationBiology--Cellen_US
dc.subject.classificationBiology--Molecularen_US
dc.subject.classificationNeuroscienceen_US
dc.titleThe Glyoxalase 1 – Methylglyoxal Pathway Regulates Neurite Development of Cerebral Cortical Neurons in the Mammalian Brainen_US
dc.typemaster thesisen_US
thesis.degree.disciplineMedicine – Biochemistry and Molecular Biologyen_US
thesis.degree.grantorUniversity of Calgaryen_US
thesis.degree.nameMaster of Science (MSc)en_US
ucalgary.item.requestcopytrueen_US
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